ABSTRACT
Vacuolar H+-ATPase (V-ATPase) is a multi-subunit proton pump that utilizes ATP hydrolysis to pump protons into the vacuole [1-
3]. V-ATPase is essential for maintaining homeostasis in acid and
base balances [4-6]. Acid and base homeostasis is critical for a
number of cellular functions including endocytosis, the trafficking
of lysosomal enzymes to lysosomes and the degradation of signaling
molecules in lysosomes [4, 7]. V-ATPase is also important for
the storage of glycogen and the sorting of the vacuole-resident
protein, carboxypeptidase Y but is not required for the delivery
of autophagosomes to the vacuole [8-11]. In addition to the well-
established role of V-ATPase in acidifying organelles, it also forms a
trans-V0 complex fusion pore during homotypic vacuolar fusion in
yeast [12, 13]. While V-ATPase has many important functions, the
possible link of this complex with diabetes has recently emerged
[14, 15]. For example, V-ATPase is necessary for exocytosis of
GLUT4-containing vesicles (glucose transporter 4) during insulin
stimulation [16]. Therefore, a better understanding of howV-ATPase
functions may shed light on how insulin stimulates the transport of
glucose and how defects in V-ATPase contribute to insulin resistance
and the development of diabetes.
